Immunological role of platelets in Theiler’s virus-induced inflammatory demyelinating disease and myocarditis

Platelets have been immunologically associated with viral and immune-mediated diseases such as Severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) and Experimental autoim-mune encephalomyelitis (EAE). However, the role of platelets in Theiler’s murine encephalo-myelitis virus (TMEV)-induced myocarditis and inflammatory demyelination disease (IDD) is still unknown. We determine whether platelets were associated with TMEV infection and whether glycoprotein Ib alpha chain (GPIbα/CD42b) antibody injection could affect the pathogenicity of TMEV-induced myocarditis and TMEV-IDD. We conducted a mechanistic experiment by injecting TMEV-infected mice with the anti-GPIbα antibodies 0 and 5 days p.i. (“Early” group) or 18 and 22 days p.i. (“Late” group). Using in silico and in vivo approaches, we found platelets and platelet-related genes were associated with TMEV infection. Platelet depletion in Early and Late mice reduced fibrotic area in the heart, inflammatory demyelinating lesions with lower viral persistence in the CNS and altered antiviral antibody responses. Thus, platelets contribute to the pathogenesis of TMEV infection by promoting fibrosis and CNS inflammation. Platelet-depletion treatment might open new therapeutic approaches for TMEV-induced myocarditis and TMEV-IDD.